The auditory P300 component of ERPs elicited during the oddball paradigm in type 2 diabetic patients

Research Article | DOI: https://doi.org/10.31579/2641-8975/005

The auditory P300 component of ERPs elicited during the oddball paradigm in type 2 diabetic patients

  • H J Teede 1*
  • S L Kozica 1
  • C B Lombard 1
  • D Ilic 1
  • S Ng 1
  • C L Harrison 1
  • 1* University of Pittsburgh Diabetes Institute, Australia.

*Corresponding Author: H J Teede, University of Pittsburgh Diabetes Institute, Australia.

Citation: H J Teede, S L Kozica, C B Lombard, D Ilic, S Ng, C L Harrison, The auditory P300 component of ERPs elicited during the oddball paradigm in type 2 diabetic patients, DOI: 10.31579/2641-8975/005

Copyright: © 2018 H J Teede.et.al.This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received: 02 August 2018 | Accepted: 14 August 2018 | Published: 24 August 2018

Keywords: Keywords

Abstract

Background: There is increasing interest in the impact of diabetes mellitus on cognitive functioning. Several studies found evidence of decreased cognitive performance in type 2 diabetics (T2DM). Since the P300 component of event-related potentials (ERPs) provides valuable information concerning cognition, we studied this component of ERPs in T2DM.

Methods: Auditory P300 event-related potentials (P300) were elicited in 43 T2DM patients and 29 age and sex-matched healthy volunteers by use of the auditory oddball paradigm, taking into account the age of the subjects, disease duration and the metabolic control.

Results: Compared with controls, diabetics had significantly longer P300 latencies (F= 5.05, p= 0.026) and lower P300 amplitudes both in Cz and Pz electrode positions (F= 8.01, p= 0.005 and F= 13.67, p= 0.000 respectively). In addition, a significant inverse correlation between P300 latency and amplitude was observed in diabetics both in Cz and Pz electrode positions (r= -0.43, p= 0.003 and r= -0.39, p= 0.01 respectively), whereas essentially no relationship between amplitude and latency was observed for the control group. N200 and P300 latencies and the reduction in their amplitudes in Cz and Pz leads were not related to either disease duration or metabolic control.

Conclusions: The observed electrophysiological abnormalities may reflect impairment of information processing and working memory, possibly associated with an accelerated ageing process. Our findings suggest that surface-recorded ERPs may be useful for detecting and monitoring the changes in brain function associated with diabetes mellitus.

Background

Diabetes mellitus is the most common metabolic disorder in man and is associated with structural and functional alterations in various organs, including the central nervous system. There is increasing interest in the impact of diabetes mellitus on cognitive functions. Since the prevalence of type 2 diabetes mellitus (T2DM) increases with age and normal aging is associated with mild deterioration in cognition, the interplay between the aging process and the duration and magnitude of hyperglycaemia is expected to result in an accelerated cognitive decline. Indeed, previous studies have indicated that older people with T2DM have a higher risk of cognitive dysfunction or dementia [1]. Moreover, epidemiological studies have shown that T2DM is strongly associated with an increased risk for AD [2].

Event-related potentials (ERPs) provide a non invasive method of studying brain neural activity with a temporal resolution reflecting the speed of cognitive processes. The P300 wave is the most studied ERP component and is considered cognitive because it is generated when subjects attend and discriminate stimuli that differ from one another on some dimension and are presented unequally in a random fashion. It is a broad, positive potential with maximal amplitudes at parietal and central midline recording sites and a peak latency of about 300–600ms. P300 latency is considered an index of the relative timing of the stimulus evaluation process [3], and P300 amplitude is believed to reflect attentional resource allocation [4]. It has been suggested that P300 is produced by interactions between frontal lobe and hippocampal/temporoparietal procedures [5].

P300 has been used extensively in investigations of psychiatric and neurological disorders involving cognitive abilities. Alterations of its latency and amplitude have been described, appearing to reflect deficits in cognitive processing [6-8]. Several studies have revealed an electrophysiological evidence of cognitive dysfunction in diabetes, even in the absence of clinical signs of central nervous system damage [9-15]. Additionally, P300 has been shown to be more sensitive in detecting cognitive deficits than psychometric tests in T2DM [9]. However, conflicting results have been reported regarding the correlation of ERPs abnormalities with clinical parameters in diabetics [9-15].

Thus, the purpose of the present study was to investigate the effect of type 2 diabetes mellitus on cognitive functioning, using auditory P300 ERP as an assessment tool and to examine the relationship of P300 to duration of disease and short-term metabolic control.

Patients and methods

Patients

A total of 72 subjects were enrolled in this study conducted by the first department of Neurology of Athens National University. The patient group comprised 43 (M:23, F:20) individuals with type 2 diabetes mellitus (39-72 years old), which were recruited from the department of Clinical Therapeutics of Athens National University. All T2DM patients met the diagnostic criteria proposed by the American Diabetes Association (ADA) [16]. Exclusion criteria were prior history of hypoglycaemic episodes, major head injury, neurosurgical operations, alcohol or drug abuse, signs or symptoms of stroke or any neurological illnesses other than diabetic neuropathy, hearing impairment, use of medication other than hypoglycaemic agents and Mini Mental State Examination score

Methods

Electrophysiological tests were performed on all of the diabetic patients in the morning between 9 and 10 a.m., after taking breakfast. Blood glucose levels were determined at the time of electrophysiological testing, to ensure absence of hypoglycaemia. HbA1c levels were measured within 7 days of test performance.

To obtain ERPs, subjects underwent a 2-tone auditory discrimination task (oddball paradigm). Two types of tones, 2000 Hz (target tone) and 1000 Hz (non-target tone), were delivered binaurally through earphones at 60 dB SPL (10 ms rise/fall, 50 ms plateau) with a rate of 1.1/s. Subjects were sitting with their eyes closed while stimuli were given, to minimize eye movements and blinking. They were asked to count silently the infrequent target tones, which presented randomly with a 0.20 probability in a series of the non-target tones, and to report the number of target tones at the end of each run. Before ERPs were recorded, the subjects completed a number of trials until they understood the different tones and the requirements of the test. EEG activity was recorded with 16 Ag-AgCl electrodes filled with paste, according to the International 10-20 system, attached to the scalp with collodion, with the linked cheeks processes and forehead serving as the reference and the ground, respectively. Electrode impedance was kept below 2 KΩ and the filter band was set at 0.1-30 Hz. The electrode positions used were F3, F4, F7, F8, T3, T4, T5, T6, C3, Cz, C4, P3, Pz, P4, O1, O2. The signal was amplified 20,000 times, the measurement epoch was 1024 ms and the sampling rate was 128 Hz per channel. Neural responses to the 2 types of stimuli were averaged separately on line and processed into voltage maps by a commercial 16 channel (Bio-Logic System Corp. Brain Atlas III) apparatus. Trials including artifacts were automatically rejected from the averages. The procedure was terminated after 35 averaged target stimuli. Each test was performed twice in order to demonstrate consistency of the waveforms. Latencies and amplitudes on each ERP component were measured from the waveforms of the first trial.

Peak latencies and baseline to peak amplitudes of N100, P200, N200 and P300 were evaluated. The P300 was identified as the highest positive peak between 250 and 600 ms after the warning stimulus (Figure 1 ).

Figure 1: P300 waveforms in response to rare (target) stimuli obtained from a 53-year-old type 2 diabetic patient. The actual P300 wave latency was 348 ms.

Peak amplitudes were measured, relative to the mean amplitude of the 100 ms pre-stimulus baseline period, and latency measurements were computed relative to stimulus onset. The earliest components N100, P200 and N200 were determined in a similar way, defined as the most negative or positive peak within the latency windows of 75-150, 150-250 and 190-360ms poststimulus, respectively [17]. Latencies of the N100 and P200 components were obtained from the non-target stimulus bank, whereas latencies of the N200 and P300 from the target stimulus bank.

Statistical analysis

Descriptive statistics are expressed as mean and ± SDs or SEs. Since the P300 latency has been reported to be prolonged in accordance with age [18], regression analysis was used to calculate the regression equation between P300 latency and age both in diabetics and controls. Analysis of covariance (ANCOVA) was used to compare the N100, P200, N200 and P300 latencies and amplitudes between controls and diabetics, using age as covariate. Pearson's correlation coefficient was calculated to assess the relationship between P300 latency and amplitude both in the control group and the patients. Pearson's correlation coefficients (r) were also used to assess the relationship between P300 latency/amplitude and disease duration as well as between P300 latency and HbA1c levels. Results were considered significant at the 0.05 level.

Results

The demographic, clinical characteristics and laboratory findings of patients and controls are summarized in (Table 1).

Table 1 Clinical, demographic characteristics and laboratory findings of patients and controls

A statistically significant positive linear correlation between P300 latency and age was observed in the patients but not in the control group. In diabetics, the slope of the latency/age regression line was 2.56 ms/year (t-test value= 3.81, p= 0.0005) whereas in the control group the corresponding slope was 0.64 (t-test value= 1.08, p= 0.29). Compared with controls, diabetics had significantly longer P300 latencies (F= 5.05, p= 0.026) and lower P300 amplitudes both in Cz and Pz electrode positions (F= 8.01, p= 0.005 and F= 13.67, p= 0.000 respectively, (Table 2 )

Table 2. Latencies (mean ± SE, ms) and amplitudes [mean ± SE or mean (SD), μV] of N1, P2, N2, and P3 in diabetics and controls.

In the diabetics, no clear correlation was found between P300 latency and duration of the disease (r= -0.082, p=0.601). No significant correlation was observed between disease duration and P300 amplitude both in Cz and Pz electrode positions (r= -0.172, p=0.269 and r= -0.282, p=0.067 respectively). Similarly, no statistically significant correlation was found between the HbA1C level, the index of the diabetic control over the previous 2–3 months and P300 latency (r= 0.159, p= 0.384) as well as P300 amplitude both in Cz and Pz electrode positions (r= -0.170, p=0.388 and r= -0.226, p=0.248 respectively). Likewise, neither clear correlation was found between N200 latency and disease duration (r= -0.058, p=0.770) or HbA1C level (r= -0.186, p=0.433), nor between N200 amplitude in Cz and Pz and disease duration (r= 0.108, p=0.593 and r= -0.108, p=0.599 respectively) or HbA1C level (r= -0.234, p=0.336 and r= -0.194, p=0.440 respectively).

Discussion

The present study examined the auditory P300 component of ERPs elicited during the oddball paradigm in type 2 diabetic patients. Compared with control subjects, the patient group showed significantly prolonged N200 and P300 latencies and significantly lower P300 amplitudes at the Cz and Pz leads. In previous studies, auditory P300 latencies in diabetics were either significantly prolonged [11-15], or tended to be prolonged [10], compared with controls. Concerning the amplitude of P300 the data are sparse. Most authors did not report measurements of amplitude [10-14], whereas others found no statistically significant difference in patients as compared to controls [15]. Abnormalities of the earlier ERP component N200 were also found in some studies [11,13], whereas in others no statistically significant difference between patients and controls was reported [15]. Additionally, in the present study, an inverse correlation of P300 latency with amplitude was shown in patients, whereas essentially no relationship between amplitude and latency was observed for the control group, a relation that has not been previously reported.

Although event-related potentials are considered an electrophysiological index of cognitive performance, knowledge of the relationship between ERP parameters and specific cognitive function domains is limited. The N100 and P200 components are believed to reflect the activity in neural areas that are activated by sensory modality and are independent of the subject's attention [19] whereas the N200 component is related to the unexpectedness of the stimulus and is regarded as a measure of the time of early stimulus processing, engaging orientation and attention [20]. With regard to P300, it is considered a reflection of memory storage operations that are initiated in the hippocampus, which is claimed to be the P300 generator [5]. The P300 latency is regarded as a measure of stimulus classification speed [21], reflecting the allocation of attentional resources for memory operations [22], whereas the P300 amplitude represents on-line updating of working memory and/or attentional processes involved in working memory [23]. Since the latencies of N100 and P200 did not differ between patients and controls, the prolongation of the N200 and P300 latencies found in the present study could not be attributed to delay in perceptual encoding. Therefore, the prolongation of the N200 latency might be associated with decline in attention and early stimulus processing, whereas the P300 abnormalities with difficulties in stimulus classification speed and working memory [24].

As far as cognitive impairment in diabetics is concerned, recent works report association between type 2 diabetes and greater decline in global cognitive performance as well as in specific cognitive function domains (memory, speed of cognitive processes, and mental flexibility) in middle-aged individuals, indicating that accelerated brain ageing might be present in T2DM patients [25-26]. Specifically, it has been suggested that decline in speed of cognitive processes is greater during the early stages of diabetes, whereas affection of memory is unremitting [25]. Considering that P300 latency reflects the speed of neuronal events underlying information processing and that P300 amplitude is associated with attention and short-term memory, our electrophysiological data appear to be in line with these neuropsychological findings.

Although diabetes mellitus is thought to be an important factor contributing to premature loss of cognitive abilities in older individuals, the putative pathogenetic mechanisms have not been fully elucidated [27]. In the present study no significant correlation between N200 and P300 latency or amplitude in Cz and Pz and either disease duration or short-term metabolic control, as it is reflected in HbA1c level, was revealed, in line with previous studies [11-14]. Given that decline in speed of cognitive processes is greater during the early stages of diabetes [25], the absence of correlation of N200 and P300 latencies and amplitudes with disease duration is not surprising. Despite the lack of any correlation between the clinical parameters of diabetes and the observed event-related potential abnormalities, it is plausible to assume that chronic sustained hyperglycaemia, might have accounted for the occurrence of the electrophysiological deficits. Hyperglycaemia has potentially toxic effects on neurons in the brain through osmotic insults, oxidative stress mediated free radical formation, increased release of inflammatory cytokines and non enzymatic glycosylation which irreversibly modifies tissue proteins and organ functions [28]. Moreover, chronic hyperglycemia is thought to contribute to reduced hippocampal neurogenesis and consequently hippocampal atrophy and cell death [29]. In support to these observations, in a recent resting-state functional magnetic resonance imaging study, it was provided evidence of reduced functional hippocampal connections bilaterally to widespread regions in T2DM patients compared to healthy controls [30]. Additionally, it has been suggested that connections between the P300 generators, i.e. the white matter volume, have a more profound impact on P300 than the size of the generators themselves [31]. Since P300 is thought to be produced by interactions between frontal lobe and hippocampal/temporal–parietal processes [5] it could be hypothesized that the P300 abnormalities in T2DM reported in the present study, might possibly reflect these neuropathological and functional alterations associated with the hippocampal circuitry, which is involved in learning and working memory. Should P300 be proved a reliable index of central nervous system dysfunction in diabetes mellitus and more sensitive than neuropsychologica1 testing, it could be used to prospectively evaluate the effects of therapeutic interventions on cognitive function in type 2 diabetes mellitus.

Conclusions

We showed prolonged latency of N200 and P300 and reduced P300 amplitude inversely correlated with P300 latency, at central midline brain area, in T2DM, without any association with disease duration or short-term metabolic control. The observed electrophysiological abnormalities may reflect impairment of attention, short-term memory and speed of information processing, possibly indicating an accelerated ageing process in diabetics. Our findings suggest that surface-recorded ERPs may be useful for detecting and monitoring the changes in brain function associated with diabetes mellitus.

References

Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.

img

Virginia E. Koenig

Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.

img

Delcio G Silva Junior

Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.

img

Ziemlé Clément Méda

Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.

img

Mina Sherif Soliman Georgy

We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.

img

Layla Shojaie

The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.

img

Sing-yung Wu

Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.

img

Orlando Villarreal

Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.

img

Katarzyna Byczkowska

Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.

img

Anthony Kodzo-Grey Venyo

Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.

img

Pedro Marques Gomes

Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.

img

Bernard Terkimbi Utoo

This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.

img

Prof Sherif W Mansour

Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.

img

Hao Jiang

As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.

img

Dr Shiming Tang

Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.

img

Raed Mualem

International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.

img

Andreas Filippaios

Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

img

Dr Suramya Dhamija

Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.

img

Bruno Chauffert

I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

img

Baheci Selen

"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

img

Jesus Simal-Gandara

I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

img

Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

img

Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

img

Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

img

Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

img

S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

img

Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

img

George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

img

Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

img

Khurram Arshad